Next Generation Opto-Jasplakinolides Enable Local Remodeling of Actin Networks

The natural product jasplakinolide is widely used to stabilize F-actin. Based on extensive structure-activity relationship studies, we have developed a new generation of photoswitchable jasplakinolides that feature rationally designed red-shifted azobenzene photoswitches. Our lead compound, nOJ, can be activated with longer wavelengths in the visible range (e.g. 440-475 nm) and rapidly returns to its inactive state through thermal relaxation. nOJ enables the reversible control of F-actin dynamics, as shown through live-cell imaging, cell migration, and cell proliferation assays. Short, local irradiation with blue light resulted in highly localized and reversible actin aggregation with subcellular precision. Our optical tool can be useful in diverse fields to study actin dynamics with excellent spatiotemporal resolution.